tbuckley/cabot-search huggingface dataset:
Long-Term Exposure to Particulate Matter &lt;2.5 μm and Lung Function Change in Children with Asthma Receiving Inhaled Corticosteroids
Authors: Franziska J. Rosser, Yueh-Ying Han, Erick Forno, Theresa W. Guilbert, Leonard B. Bacharier, Wanda Phipatanakul, Gillian C. Goobie, S. Mehdi Nouraie, Mary Martinez, Juan C. Celedón
Journal: American Journal of Respiratory and Critical Care Medicine (2023)

"Long-Term Exposure to Particulate Matter <2.5 μm and Lung Function Change in Children with Asthma Receiving Inhaled Corticosteroids." American Journal of Respiratory and Critical Care Medicine, 208(5), pp. 622–624
Sleep, the Forgotten, Yet Potentially Modifiable, Dimension in Chronic Obstructive Pulmonary Disease Care
Authors: Nancy H. Stewart, Valerie G. Press, Lucas Donovan
Journal: American Journal of Respiratory and Critical Care Medicine (2023)

"Sleep, the Forgotten, yet Potentially Modifiable Dimension in COPD Care." American Journal of Respiratory and Critical Care Medicine, 0(ja), pp.
Blinatumomab Conundrum in Low-Risk Relapsed B-Cell ALL
Authors: Luke D. Maese, Michael A. Pulsipher
Journal: Journal of Clinical Oncology (2023)

The Oncology Grand Rounds series is designed to place original reports published in the Journal into clinical context. A case presentation is followed by a description of diagnostic and management challenges, a review of the relevant literature, and a summary of the authors' suggested management approaches. The goal of this series is to help readers better understand how to apply the results of key studies, including those published in Journal of Clinical Oncology, to patients seen in their own clinical practice.The Children's Oncology Group (COG) AALL1331 trial demonstrated improved survival and less toxicity in children with high-/intermediate-risk relapsed ALL receiving blinatumomab compared with intensive chemotherapy before hematopoietic stem-cell transplant (HSCT). The low-risk arm of AALL1331 compared addition of three cycles of blinatumomab to chemotherapy alone, but a survival improvement was not noted. Secondary analyses showed improvement in disease-free survival (DFS) and overall survival (OS) of low-risk patients with bone marrow disease ± extramedullary (EM) involvement (4-year DFS 72.7% ± 5.8% v 53.7% ± 6.7%; 4-year OS 97.1% ± 2.1% v 84.8% ± 4.8%), but failed to show an advantage with blinatumomab for patients with isolated EM relapse. Of note, DFS of isolated CNS (iCNS) relapse was worse than previous studies at 24% on both arms, likely because of decreases in CNS-intensive therapy compared with previous approaches and inadequacy of blinatumomab for controlling CNS disease.Our case of late isolated CNS B-cell ALL relapse outlines challenges for clinicians attempting to decrease toxicity and avoid HSCT: (1) defining of low risk appropriately, (2) attempting to reduce the treatment burden of past protocols, and (3) understanding approach and timing of cranial irradiation.Although AALL1331 therapy without blinatumomab leads to excellent survival in patients with isolated testicular relapse, we recommend a modified AALL02P2 backbone of chemotherapy with 1,800 cGy cranial radiotherapy for patients with late iCNS relapse. Future studies integrating chimeric antigen receptor T cells, which have better CNS penetration, may help decrease the intensive treatment burden for patients with late iCNS recurrence.
Market, Gift, Everyday Ethics, and Emmanuel Levinas in Patient Care
Authors: Alan B. Astrow
Journal: Journal of Clinical Oncology (2023)

A simple, and brief, human gesture may turn a routine visit into a healing encounter. We need a conceptual nudge; otherwise, we are left stranded at the lowest common denominator of value, money. Physicians work long and hard to perfect our craft, but might some element of our therapeutic abilities be seen, like the artist’s native talent, as gift? The beginning lies in a way of thinking that places protection of the vulnerable human person front and center.
The surgical patient of yesterday, today, and tomorrow—a time-trend analysis based on a cohort of 8.7 million surgical patients
Authors: Samuel Knoedler, Dany Y. Matar, Sarah Friedrich, Leonard Knoedler, Valentin Haug, Gabriel Hundeshagen, Martin Kauke-Navarro, Ulrich Kneser, Bohdan Pomahac, Dennis P. Orgill, Adriana C. Panayi
Journal: International Journal of Surgery (2023)

Background: Global healthcare delivery is challenged by the aging population and the increase in obesity and type 2 diabetes. The extent to which such trends affect the cohort of patients the authors surgically operate on remains to be elucidated. Comprising of 8.7 million surgical patients, the American College of Surgeons (ACS) National Surgical Quality Improvement Program (NSQIP) database can be analyzed to investigate the echo of general population dynamics and forecast future trends. Material and methods: The authors reviewed the ACS-NSQIP database (2008–2020) in its entirety, extracting patient age, BMI, and diabetes prevalence. Based on these data, the authors forecasted future trends up to 2030 using a drift model. Results: During the review period, median age increased by 3 years, and median BMI by 0.9 kg/m 2 . The proportion of patients with overweight, obesity class I, and class II rates increased. The prevalence of diabetes rose between 2008 (14.9%) and 2020 (15.3%). The authors forecast the median age in 2030 to reach 61.5 years and median BMI to climb to 29.8 kg/m 2 . Concerningly, in 2030, eight of ten surgical patients are projected to have a BMI above normal. Diabetes prevalence is projected to rise to 15.6% over the next decade. Conclusion: General population trends echo in the field of surgery, with the surgical cohort aging at an alarmingly rapid rate and increasingly suffering from obesity and diabetes. These trends show no sign of abating without dedicated efforts and call for urgent measures and fundamental re-structuring for improved future surgical care.
Specific Respiratory System Compliance in COVID-19 and Non–COVID-19 Acute Respiratory Distress Syndrome
Authors: Tommaso Pozzi, Francesca Collino, Serena Brusatori, Federica Romitti, Mattia Busana, Onnen Moerer, Luigi Camporota, Davide Chiumello, Silvia Coppola, Luciano Gattinoni
Journal: American Journal of Respiratory and Critical Care Medicine (2023)

"Specific Respiratory System Compliance in COVID-19 and Non COVID-19 ARDS." American Journal of Respiratory and Critical Care Medicine, 0(ja), pp.
Large Vessel Vasculitis in a Young Woman with EIF2AK4-associated Pulmonary Capillary Hemangiomatosis/Pulmonary Veno-Occlusive Disease
Authors: Despina Michailidou, Delphine L. Chen, Bridget F. Collins, Marjorie P. George, David Montani, Samuel G. Rayner, Chanprasert Sirisak, Peter J. Leary
Journal: American Journal of Respiratory and Critical Care Medicine (2023)

"Large Vessel Vasculitis in a Young Woman with EIF2AK4-associated Pulmonary Capillary Hemangiomatosis/Pulmonary Veno-Occlusive Disease." American Journal of Respiratory and Critical Care Medicine, 208(5), pp. e29–e31
Subphenotypes Assigned to Pediatric Acute Respiratory Failure Patients Show Differing Outcomes
Authors: Heidi R. Flori, Min Zhang, Jiaheng Xie, Guangyu Yang, Anil Sapru, Carolyn S. Calfee, Kevin L. Delucchi, Pratik Sinha, Martha A. Q. Curley, Mary K. Dahmer
Journal: American Journal of Respiratory and Critical Care Medicine (2023)

"Subphenotypes Assigned to Pediatric Acute Respiratory Failure Patients Show Differing Outcomes." American Journal of Respiratory and Critical Care Medicine, 0(ja), pp.
Finding the Right Biological: Eosinophil Subset Differences in Asthma and Chronic Obstructive Pulmonary Disease
Authors: Christine M. Freeman, Jeffrey L. Curtis, Annette T. Hastie
Journal: American Journal of Respiratory and Critical Care Medicine (2023)

"Finding the Right Biological: Eosinophil Subset Differences in Asthma and COPD." American Journal of Respiratory and Critical Care Medicine, 0(ja), pp.
A Pathology-based Case Series of Influenza- and COVID-19–associated Pulmonary Aspergillosis: The Proof Is in the Tissue
Authors: Lore Vanderbeke, Cato Jacobs, Simon Feys, Agustin Reséndiz-Sharpe, Yves Debaveye, Greet Hermans, Stephanie Humblet-Baron, Katrien Lagrou, Philippe Meersseman, Marijke Peetermans, Laura Seldeslachts, Arno Vanstapel, Greetje Vande Velde, Eric Van Wijngaerden, Alexander Wilmer, Erik Verbeken, Gert De Hertogh, Joost Wauters
Journal: American Journal of Respiratory and Critical Care Medicine (2023)

Invasive pulmonary aspergillosis has emerged as a frequent coinfection in severe coronavirus disease (COVID-19), similarly to influenza, yet the clinical invasiveness is more debated.
Abstract P523: Joint Improvement Scale of Loneliness and Traditional Risk Factor Control, and Incident Cardiovascular Disease in Diabetes Patients
Authors: Xuan Wang, Hao Ma, Xiang Li, Yoriko Heianza, Vivian A Fonseca, Lu Qi
Journal: Circulation (2023)

Background: Emerging evidence has shown a higher rate of loneliness and social isolation among patients with diabetes, and loneliness and isolation has been associated with high risk of cardiovascular disease (CVD). Hypothesis: We investigated the extent to which the risks of CVDs could be lowered by improvement of loneliness and social isolation, individually or in conjunction with controlling traditional risk factors in diabetic patients. Methods: A total of 18,783 participants diagnosed with diabetes from the UK Biobank were included. A two-item scale and a three-item scale were used to assess the improvement of loneliness and isolation status, respectively. The degree of traditional risk-factor control was defined as the number of glycated hemoglobin (HbA1c), blood pressure (BP), low-density-lipoprotein cholesterol (LDL-C), smoking and microalbumin reaching the target range. Results: During a mean follow-up of 10.7 years, 3,129 incident total CVD events were documented, including 2,627 coronary heart disease (CHD) and 721 stroke. We found that each point increase in loneliness improvement scale was significantly associated with an 11% lower risk of CVD (HR, 95%CI, 0.89, 0.84-0.93) and a 12% lower risk of CHD (HR, 95%CI, 0.88, 0.83-0.93), but not with stroke. The improvement scale of social isolation was not associated with CVDs. Loneliness showed greater relative importance than lifestyle risk factors in preventing CVD among diabetic patients. We found a significant additive interaction between loneliness and the degree of traditional risk-factor control on the risk of CVDs ( P for additive interaction=0.002). Moreover, compared with non-diabetes controls, the diabetes-related excess CVD risk might be eliminated when three or more risk factors were controlled in non-lonely patients, but more than four are required in lonely patients. Conclusion: Among diabetes patients, improvement of loneliness is associated with a lower risk of CVD and shows an additive interaction with traditional risk factor control.
All‐in‐One Heptamethine Cyanine Amphiphiles for Dual Imaging‐Guided Chemo‐Photodynamic‐Photothermal Therapy of Breast Cancer
Authors: Yu Li, Jing Zhang, Lijun Zhu, Mou Jiang, Changsheng Ke, Hanxiong Long, Ruoyun Lin, Chaohui Ye, Xin Zhou, Zhong‐Xing Jiang, Shizhen Chen
Journal: Advanced Healthcare Materials (2023)

Developing a theranostic system that integrates multimodal imaging, synergistic therapeutic, and formulation entities is a promising strategy for efficient cancer treatment. However, the complexity and safety concerns of multiple functional entities hinder their clinical translation. Herein, versatile "all-in-one" heptamethine cyanine amphiphiles (PEG-Cy-Fs) with multiple favorable capabilities, including fluorine-19 magnetic resonance imaging (19 F MRI), near-infrared fluorescence imaging (NIR FLI), photodynamic therapy (PDT), photothermal therapy (PTT), polyethylene glycolation (PEGylation) and high biocompatibility, are developed for the convenient construction of theranostic platforms. Amphiphiles PEG-Cy-Fs are synthesized on a multi-hundred-milligram scale with high efficacy, which self-assembled with a chemotherapy drug tamoxifen (TAM) into monodisperse and stable nanoparticles (SoFoTm/PEG-Cy-F18 ) with "turned on" FLI, sensitive 19 F MRI, mitochondria-targeting ability, high PDT and PTT efficacy, and PEGylation-optimized pharmacokinetics. The selective accumulation of SoFoTm/PEG-Cy-F18 in xenograft MCF-7 tumor with a long retention time (>10 days) enabled 19 F MRI-NIR FLI-guided chemo-photodynamic-photothermal therapy (chemo-PDT-PTT) of breast cancer with high therapeutical index in mice. The "all-in-one" heptamethine cyanine amphiphile may facilitate the convenient and standardized preparation of high-performance theranostics systems for clinical translation.
Synergistic Photochemo Effects Based on Light‐Activatable Dual Prodrug Nanoparticles for Effective Cancer Therapy
Authors: Zhi‐Yong Liu, Guobo Chen, Xiang Wang, Ru-Chen Xu, Fu Wang, Zhuo‐Ran Qi, Jia‐Lei Sun, Guang‐Cong Zhang, Yuqing Miao, Xi‐Zhong Shen, Ji‐Min Zhu, Shu‐Qiang Weng, Hong Chen, Yuhao Li
Journal: Advanced Healthcare Materials (2023)

Ferroptosis is identified as a novel type of cell death with distinct properties involved in physical conditions and various diseases, including cancers. It is considered that ferroptosis provides a promising therapeutic strategy for optimizing oncotherapy. Although erastin is an effective ferroptosis trigger, the potential of its clinical application is largely restricted by its poor water solubility and concomitant limitations. To address this issue, an innovative nanoplatform (PE@PTGA) that integrated protoporphyrin IX (PpIX) and erastin coated with amphiphilic polymers (PTGA) to evoke ferroptosis and apoptosis is constructed and exemplified using an orthotopic hepatocellular carcinoma (HCC) xenograft mouse model as a paradigm. The self-assembled nanoparticles can enter HCC cells and release PpIX and erastin. With light stimulation, PpIX exerts hyperthermia and reactive oxygen species to inhibit the proliferation of HCC cells. Besides, the accumulated reactive oxygen species (ROS) can further promote erastin-induced ferroptosis in HCC cells. In vitro and in vivo studies reveal that PE@PTGA synergistically inhibits tumor development by stimulating both ferroptosis- and apoptosis-related pathways. Moreover, PE@PTGA has low toxicity and satisfactory biocompatibility, suggesting its promising clinical benefit in cancer treatments.
PTEN Loss Confers Resistance to Anti–PD-1 Therapy in Non–Small Cell Lung Cancer by Increasing Tumor Infiltration of Regulatory T Cells
Authors: Francisco Exposito, Miriam Redrado, Maeva Houry, Katherine Hastings, Magdalena Molero-Abraham, Teresa Lozano, Jose Luis Solorzano, Julian Sanz-Ortega, Vera Adradas, Ramon Amat, Esther Redin, Sergio Leon, Naroa Legarra, Javier Garcia, Diego Serrano, Karmele Valencia, Camila Robles-Oteiza, Giorgia Foggetti, Nerea Otegui, Enriqueta Felip, Juan J. Lasarte, Luis Paz-Ares, Jon Zugazagoitia, Katerina Politi, Luis Montuenga, Alfonso Calvo
Journal: Cancer Research (2023)

Immunotherapy resistance in non-small cell lung cancer (NSCLC) may be mediated by an immunosuppressive microenvironment, which can be shaped by the mutational landscape of the tumor. Here, we observed genetic alterations in the PTEN/PI3K/AKT/mTOR pathway and/or loss of PTEN expression in >25% of patients with NSCLC, with higher frequency in lung squamous carcinomas (LUSC). Patients with PTEN-low tumors had higher levels of PD-L1 and PD-L2 and showed worse progression-free survival when treated with immunotherapy. Development of a Pten-null LUSC mouse model revealed that tumors with PTEN loss were refractory to antiprogrammed cell death protein 1 (anti-PD-1), highly metastatic and fibrotic, and secreted TGFβ/CXCL10 to promote conversion of CD4+ lymphocytes into regulatory T cells (Treg). Human and mouse PTEN-low tumors were enriched in Tregs and expressed higher levels of immunosuppressive genes. Importantly, treatment of mice bearing Pten-null tumors with TLR agonists and anti-TGFβ antibody aimed to alter this immunosuppressive microenvironment and led to tumor rejection and immunologic memory in 100% of mice. These results demonstrate that lack of PTEN causes immunotherapy resistance in LUSCs by establishing an immunosuppressive tumor microenvironment that can be reversed therapeutically.PTEN loss leads to the development of an immunosuppressive microenvironment in lung cancer that confers resistance to anti-PD-1 therapy, which can be overcome by targeting PTEN loss-mediated immunosuppression.
Targeting KDM2A Enhances T-cell Infiltration in NSD1-Deficient Head and Neck Squamous Cell Carcinoma
Authors: Chen Chen, June Ho Shin, Zhuoqing Fang, Kevin Brennan, Nina B. Horowitz, Kathleen L. Pfaff, Emma L. Welsh, Scott J. Rodig, Olivier Gevaert, Or Gozani, Ravindra Uppaluri, John B. Sunwoo
Journal: Cancer Research (2023)

Abstract In head and neck squamous cell carcinoma (HNSCC), a significant proportion of tumors have inactivating mutations in the histone methyltransferase NSD1. In these tumors, NSD1 inactivation is a driver of T-cell exclusion from the tumor microenvironment (TME). A better understanding of the NSD1-mediated mechanism regulating infiltration of T cells into the TME could help identify approaches to overcome immunosuppression. Here, we demonstrated that NSD1 inactivation results in lower levels of H3K36 dimethylation and higher levels of H3K27 trimethylation, the latter being a known repressive histone mark enriched on the promoters of key T-cell chemokines CXCL9 and CXCL10. HNSCC with NSD1 mutations had lower levels of these chemokines and lacked responses to PD-1 immune checkpoint blockade. Inhibition of KDM2A, the primary lysine demethylase that is selective for H3K36, reversed the altered histone marks induced by NSD1 loss and restored T-cell infiltration into the TME. Importantly, KDM2A suppression decreased growth of NSD1-deficient tumors in immunocompetent, but not in immunodeficient, mice. Together, these data indicate that KDM2A is an immunotherapeutic target for overcoming immune exclusion in HNSCC. Significance: The altered epigenetic landscape of NSD1-deficient tumors confers sensitivity to inhibition of the histone-modifying enzyme KDM2A as an immunotherapeutic strategy to stimulate T-cell infiltration and suppress tumor growth.
Platelet‐Membrane‐Coated Polydopamine Nanoparticles for Neuroprotection by Reducing Oxidative Stress and Repairing Damaged Vessels in Intracerebral Hemorrhage
Authors: Canxin Xu, Yuanbo Pan, Hongchi Zhang, Yuhao Sun, Yi Cao, Pengfei Qi, Mingli Li, Ozioma Udochukwu Akakuru, Lulu He, Chen Xiao, Bomin Sun, Liuguan Bian, Juan Li, Aiguo Wu
Journal: Advanced Healthcare Materials (2023)

Intracerebral hemorrhage (ICH) has a high morbidity and mortality rate. Excessive reactive oxygen species (ROS) caused by primary and second brain injury can induce neuron death and inhibit neurological functional recovery after ICH. Therefore, exploring an effective way to noninvasively target hemorrhage sites to scavenge ROS is urgently needed. Inspired by the biological function of platelets to target injury vessel and repair injury blood vessels, platelet-membrane-modified polydopamine (Menp@PLT) nanoparticles are developed with targeting to hemorrhage sites of ICH. Results demonstrate that Menp@PLT nanoparticles can effectively achieve targeting to the location of intracranial hematoma. Furthermore, Menp@PLT with excellent anti-ROS properties can scavenge ROS and improve neuroinflammation microenvironment of ICH. In addition, Menp@PLT may play a role in decreasing hemorrhage volume by repairing injury blood vessels. Combining platelet membrane and anti-ROS nanoparticles for targeting brain hemorrhage sites provide a promising strategy for efficiently treating ICH.
Migraine and risk of premature myocardial infarction and stroke among men and women: A Danish population-based cohort study
Authors: Cecilia Hvitfeldt Fuglsang, Lars Pedersen, Morten Schmidt, Jan P. Vandenbroucke, Hans Erik Bøtker, Henrik Toft Sørensen
Journal: PLoS Medicine (2023)

Migraine carries risk of myocardial infarction (MI) and stroke. The risk of premature MI (i.e., among young adults) and stroke differs between men and women; previous studies indicate that migraine is mainly associated with an increased risk of stroke among young women. The aim of this study was to examine impact of migraine on the risk of premature (age ≤60 years) MI and ischemic/hemorrhagic stroke among men and women.
Tissue‐Engineered Cochlear Fibrosis Model Links Complex Impedance to Fibrosis Formation for Cochlear Implant Patients
Authors: Simone R. de Rijk, Alexander J. Boys, Iwan V. Roberts, Chen Jiang, Charlotte Garcia, Róisín M. Owens, Manohar Bance
Journal: Advanced Healthcare Materials (2023)

Cochlear implants are a life-changing technology for those with severe sensorineural hearing loss, partially restoring hearing through direct electrical stimulation of the auditory nerve. However, they are known to elicit an immune response resulting in fibrotic tissue formation in the cochlea that is linked to residual hearing loss and suboptimal outcomes. Intracochlear fibrosis is difficult to track without postmortem histology, and no specific electrical marker for fibrosis exists. In this study, a tissue-engineered model of cochlear fibrosis is developed following implant placement to examine the electrical characteristics associated with fibrotic tissue formation around electrodes. The model is characterized using electrochemical impedance spectroscopy and an increase in the resistance and a decrease in capacitance of the tissue using a representative circuit are found. This result informs a new marker of fibrosis progression over time that is extractable from voltage waveform responses, which can be directly measured in cochlear implant patients. This marker is tested in a small sample size of recently implanted cochlear implant patients, showing a significant increase over two postoperative timepoints. Using this system, complex impedance is demonstrated as a marker of fibrosis progression that is directly measurable from cochlear implants to enable real-time tracking of fibrosis formation in patients, creating opportunities for earlier treatment intervention to improve cochlear implant efficacy.
Nanomaterials in tumor immunotherapy: new strategies and challenges
Authors: Xudong Zhu, Shenglong Li
Journal: Molecular Cancer (2023)

Abstract Tumor immunotherapy exerts its anti-tumor effects by stimulating and enhancing immune responses of the body. It has become another important modality of anti-tumor therapy with significant clinical efficacy and advantages compared to chemotherapy, radiotherapy and targeted therapy. Although various kinds of tumor immunotherapeutic drugs have emerged, the challenges faced in the delivery of these drugs, such as poor tumor permeability and low tumor cell uptake rate, had prevented their widespread application. Recently, nanomaterials had emerged as a means for treatment of different diseases due to their targeting properties, biocompatibility and functionalities. Moreover, nanomaterials possess various characteristics that overcome the defects of traditional tumor immunotherapy, such as large drug loading capacity, precise tumor targeting and easy modification, thus leading to their wide application in tumor immunotherapy. There are two main classes of novel nanoparticles mentioned in this review: organic (polymeric nanomaterials, liposomes and lipid nanoparticles) and inorganic (non-metallic nanomaterials and metallic nanomaterials). Besides, the fabrication method for nanoparticles, Nanoemulsions, was also introduced. In summary, this review article mainly discussed the research progress of tumor immunotherapy based on nanomaterials in the past few years and offers a theoretical basis for exploring novel tumor immunotherapy strategies in the future.